Reviewed,
UniProtKB/Swiss-Prot P51797 (CLCN6_HUMAN)
Last modified
June 16, 2009.
Version 87.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Chloride transport protein 6 Short name=ClC-6 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 869 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Chloride transport protein, initially identified as voltage-gated chloride channel. The presence of the conserved gating glutamate residues suggests that is functions as antiporter. |
| Subcellular location | Endosome membrane; Multi-pass membrane protein. Note: Detected in detergent-resistant lipid rafts. |
| Tissue specificity | Testis, ovary, small intestine, brain and skeletal muscle. Low level expression in aortic and coronary vascular smooth muscle cells, and aortic endothelial cells. Isoform C is only detected in kidney. Ref.1 Ref.2 Ref.8 |
| Post-translational modification | N-glycosylated on several asparagine residues. |
| Miscellaneous | The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters By similarity. |
| Sequence similarities | Belongs to the chloride channel (TC 2.A.49) family. [View classification] Contains 2 CBS domains. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Antiport Ion transport Transport |
| Cellular component | Endosome Membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | CBS domain Repeat Transmembrane |
| Ligand | ATP-binding Chloride Nucleotide-binding |
| PTM | Glycoprotein |
| Gene Ontology (GO) | |
| Biological process | cell volume homeostasis Ref.1 Ref.2 Non-traceable author statement. Source: UniProtKB chloride transport Ref.1 Ref.2Non-traceable author statement. Source: UniProtKB signal transduction Ref.1 Ref.2Non-traceable author statement. Source: UniProtKB |
| Cellular component | integral to membrane Ref.1 Ref.2 Non-traceable author statement. Source: UniProtKB |
| Molecular function | chloride ion binding Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated chloride channel activity Ref.1 Ref.2Non-traceable author statement. Source: UniProtKB |
| Complete GO annotation... | |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform A (identifier: P51797-1) Also known as: Clc-6a; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform B (identifier: P51797-2) Also known as: ClC-6b; D2-A1; The sequence of this isoform differs from the canonical sequence as follows: 237-320: DKRDFVSAGA...LLNFGEFKCS → YGKRQERLCI...APWIAELWRV 321-869: Missing. | ||||||
| Isoform C (identifier: P51797-3) Also known as: ClC-6c; D1-A1; The sequence of this isoform differs from the canonical sequence as follows: 319-353: CSDSDKKCHLWTAMDLGFFVVMGVIGGLLGATFNC → SLREPPCVSGNHRGGVCGLDGVRRMPTDVLFESNR 354-869: Missing. | ||||||
| Isoform D (identifier: P51797-4) Also known as: ClC-6d; D1-A2; The sequence of this isoform differs from the canonical sequence as follows: 237-308: DKRDFVSAGA...QFGSWGSFQL → SGCWSCCSFR...APWIAELWRV 309-869: Missing. | ||||||
| Isoform E (identifier: P51797-5) The sequence of this isoform differs from the canonical sequence as follows: 844-869: IVGIITRHNLTYEFLQARLRQHYQTI → VSEAPALPPP...LHLRRDLRIR | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 869 | 869 | Chloride transport protein 6 | PRO_0000094449 | |||||
Regions | |||||||||
| Topological domain | 1 – 80 | 80 | Cytoplasmic By similarity | ||||||
| Transmembrane | 81 – 113 | 33 | By similarity | ||||||
| Transmembrane | 128 – 150 | 23 | By similarity | ||||||
| Transmembrane | 176 – 194 | 19 | By similarity | ||||||
| Transmembrane | 200 – 217 | 18 | By similarity | ||||||
| Transmembrane | 277 – 294 | 18 | By similarity | ||||||
| Transmembrane | 335 – 364 | 30 | By similarity | ||||||
| Transmembrane | 371 – 392 | 22 | By similarity | ||||||
| Transmembrane | 462 – 481 | 20 | By similarity | ||||||
| Transmembrane | 487 – 511 | 25 | By similarity | ||||||
| Transmembrane | 553 – 571 | 19 | By similarity | ||||||
| Topological domain | 572 – 869 | 298 | Cytoplasmic By similarity | ||||||
| Domain | 605 – 662 | 58 | CBS 1 | ||||||
| Domain | 807 – 868 | 62 | CBS 2 | ||||||
| Nucleotide binding | 630 – 632 | 3 | ATP By similarity | ||||||
| Nucleotide binding | 849 – 852 | 4 | ATP By similarity | ||||||
| Region | 159 – 166 | 8 | In-membrane helix By similarity | ||||||
| Region | 241 – 253 | 13 | In-membrane helix By similarity | ||||||
| Region | 257 – 265 | 9 | In-membrane helix By similarity | ||||||
| Region | 519 – 533 | 15 | In-membrane helix By similarity | ||||||
| Region | 534 – 536 | 3 | In-membrane loop between two helices By similarity | ||||||
| Region | 537 – 548 | 12 | In-membrane helix By similarity | ||||||
| Region | 549 – 552 | 4 | In-membrane loop between two helices By similarity | ||||||
| Motif | 156 – 160 | 5 | Selectivity filter part_1 By similarity | ||||||
| Motif | 198 – 202 | 5 | Selectivity filter part_2 By similarity | ||||||
| Motif | 487 – 491 | 5 | Selectivity filter part_3 By similarity | ||||||
| Compositional bias | 4 – 18 | 15 | Cys-rich | ||||||
Sites | |||||||||
| Binding site | 157 | 1 | Chloride By similarity | ||||||
| Binding site | 489 | 1 | Chloride; via amide nitrogen By similarity | ||||||
| Binding site | 576 | 1 | Chloride By similarity | ||||||
| Site | 200 | 1 | Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transport By similarity | ||||||
| Site | 267 | 1 | Mediates proton transfer from the protein to the inner aqueous phase By similarity | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 410 | 1 | N-linked (GlcNAc...) | ||||||
| Glycosylation | 422 | 1 | N-linked (GlcNAc...) | ||||||
| Glycosylation | 432 | 1 | N-linked (GlcNAc...) | ||||||
Natural variations | |||||||||
| Alternative sequence | 237 – 320 | 84 | DKRDF…EFKCS → YGKRQERLCISRSGCWSCCS FRGANRGYLVQSRGGFVLLE PRAHVESALLFHVCHLHPQL LPFWDSVWKLGFLPAPWIAE LWRV in isoform B. | VSP_001043 | |||||
| Alternative sequence | 237 – 308 | 72 | DKRDF…GSFQL → SGCWSCCSFRGANRGYLVQS RGGFVLLEPRAHVESALLFH VCHLHPQLLPFWDSVWKLGF LPAPWIAELWRV in isoform D. | VSP_001047 | |||||
| Alternative sequence | 309 – 869 | 561 | Missing in isoform D. | VSP_001048 | |||||
| Alternative sequence | 319 – 353 | 35 | CSDSD…ATFNC → SLREPPCVSGNHRGGVCGLD GVRRMPTDVLFESNR in isoform C. | VSP_001045 | |||||
| Alternative sequence | 321 – 869 | 549 | Missing in isoform B. | VSP_001044 | |||||
| Alternative sequence | 354 – 869 | 516 | Missing in isoform C. | VSP_001046 | |||||
| Alternative sequence | 844 – 869 | 26 | IVGII…HYQTI → VSEAPALPPPLREDPLARCC LCTQASHQKRRHPTRRGECG PTLALNPARLPCTRDPFPCL PADGTSVPLAVLSSQSRAST RLCLPPEMLLFTPYHWCSLV LHLRRDLRIR in isoform E. | VSP_017188 | |||||
| Natural variant | 198 | 1 | G → E: dbSNP rs198400. Ref.6 | VAR_023051 | |||||
Experimental info | |||||||||
| Mutagenesis | 410 | 1 | N → A: Abolishes N-glycosylation; when associated with A-422 and A-432. | ||||||
| Mutagenesis | 422 | 1 | N → A: Abolishes N-glycosylation; when associated with A-410 and A-432. | ||||||
| Mutagenesis | 432 | 1 | N → A: Abolishes N-glycosylation; when associated with A-410 and A-422. | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family." Brandt S., Jentsch T.J. FEBS Lett. 377:15-20(1995) [PubMed: 8543009] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), TISSUE SPECIFICITY. Tissue: Brain. |
| [2] | "Alternative splicing of ClC-6 (a member of the ClC chloride-channel family) transcripts generates three truncated isoforms one of which, ClC-6c, is kidney-specific." Eggermont J., Buyse G., Voets T., Tytgat J., De Smedt H., Droogmans G., Nilius B. Biochem. J. 325:269-276(1997) [PubMed: 9224655] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS B; C AND D), NUCLEOTIDE SEQUENCE [MRNA] OF 1-409 (ISOFORM A), TISSUE SPECIFICITY. Tissue: Chronic myeloid leukemia cell. |
| [3] | "Complete genomic structure of the CLCN6 and CLCN7 putative chloride channel genes." Kornak U., Boesl M.R., Kubisch C. Biochim. Biophys. Acta 1447:100-106(1999) [PubMed: 10500249] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A). |
| [4] | "Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1." Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S. DNA Res. 1:223-229(1994) [PubMed: 7584044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Tissue: Bone marrow. |
| [5] | "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION. |
| [6] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-198. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Tissue: Brain. |
| [8] | "Expression of CLCN voltage-gated chloride channel genes in human blood vessels." Lamb F.S., Clayton G.H., Liu B.-X., Smith R.L., Barna T.J., Schutte B.C. J. Mol. Cell. Cardiol. 31:657-666(1999) [PubMed: 10198195] [Abstract] Cited for: TISSUE SPECIFICITY. Tissue: Aortic endothelium and Vascular smooth muscle. |
| [9] | "Human ClC-6 is a late endosomal glycoprotein that associates with detergent-resistant lipid domains." Ignoul S., Simaels J., Hermans D., Annaert W., Eggermont J. PLoS ONE 2:E474-E474(2007) [PubMed: 17534424] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF ASN-410; ASN-422 AND ASN-432. |
Cross-references
Sequence databases | |
|---|---|
| X83378 mRNA. Translation: CAA58292.1. X96391 mRNA. Translation: CAA65255.1. X99472 Genomic DNA. Translation: CAA67835.1. X99473 mRNA. Translation: CAA67836.1. X99474 mRNA. Translation: CAA67837.1. X99475 mRNA. Translation: CAA67838.1. AF009257 AF009256 Genomic DNA. Translation: AAB69287.1. D28475 mRNA. Translation: BAA05836.4. AL953897, AL021155 Genomic DNA. Translation: CAI15891.1. AL953897, AL021155 Genomic DNA. Translation: CAI15892.1. AL953897, AL021155 Genomic DNA. Translation: CAI15893.1. AL953897, AL021155 Genomic DNA. Translation: CAI15894.1. AL953897, AL021155 Genomic DNA. Translation: CAI15895.1. AL021155, AL953897 Genomic DNA. Translation: CAI23402.1. AL021155, AL953897 Genomic DNA. Translation: CAI23403.1. AL021155, AL953897 Genomic DNA. Translation: CAI23404.1. AL021155, AL953897 Genomic DNA. Translation: CAI23405.1. AL021155, AL953897 Genomic DNA. Translation: CAI23406.1. BC117420 mRNA. Translation: AAI17421.1. BC117424 mRNA. Translation: AAI17425.1. | |
| IPI | IPI00180121. IPI00305252. IPI00395741. IPI00414669. IPI00642888. |
| PIR | S68428. |
| RefSeq | NP_001277.1. NP_068503.1. NP_068504.1. NP_068505.1. |
| UniGene | Hs.193043 |
3D structure databases | |
| ModBase | Search... |
Proteomic databases | |
| PRIDE | P51797. |
Genome annotation databases | |
| Ensembl | ENSG00000011021. Homo sapiens. [Contig view] |
| GeneID | 1185. |
| KEGG | hsa:1185. |
Organism-specific databases | |
| GeneCards | GC01P011800. |
| H-InvDB | HIX0000129. |
| HGNC | HGNC:2024. CLCN6. |
| MIM | 602726. gene. |
| PharmGKB | PA26551. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | P51797. |
Gene expression databases | |
| ArrayExpress | P51797. |
| Bgee | P51797. |
Family and domain databases | |
| InterPro | IPR014743. Cl-channel_core. IPR001807. Cl-channel_volt. IPR002248. Cl_channel6. IPR000644. Cysta_beta_synth_core. [Graphical view] |
| Gene3D | G3DSA:1.10.3080.10. Cl-channel_core. 1 hit. |
| PANTHER | PTHR11689. Cl-channel_volt. 1 hit. |
| Pfam | PF00571. CBS. 1 hit. PF00654. Voltage_CLC. 1 hit. [Graphical view] |
| PRINTS | PR00762. CLCHANNEL. PR01117. CLCHANNEL6. |
| SMART | SM00116. CBS. 2 hits. [Graphical view] |
| PROSITE | PS51371. CBS. 2 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 4898. |
| SOURCE | Search... |
Entry information
| Entry name | CLCN6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P51797 Secondary accession number(s): O60818 Q99429 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


